Anti-Diarrhea Agents

Question 1

Examples of Opioid agonists, Bile-acid sequestrants, Bismuth, Octreotide and Somatostatin

Answer 1

Opioid agonists: Loperamide, Diphenoxylate and difenoxin

Bile-acid sequestrants: Cholestyramine,
colestipol, colesevalam

Bismuth: Bismuth subsalicylate, Bismuth subcitrate
potassium

Octreotide and Somatostatin: Octreotide and Somatostatin

Question 2

Loperamide

Answer 2

Type: Opioid Agonist

MOA: µ-receptor activity
– decease Peristaltic contraction
– increase Segmental contractions
– increase Small intestinal and mouth to cecum transit time
– increase Anal sphincter tone
– Anti-secretory activity against cholera toxin and E.coli
toxin

PK: Penetrates the brain, but pumped out again

Use: Travelers diarrhea, Acute and chronic diarrhea

AES: Constipation, Abdominal pain

Question 3

Diphenoxylate and difenoxin

Answer 3

Type: Opioid Agonists

***Higher dose = CNS effect (Atropine to discourage overuse)

Use: Diarrhea

AES:
CNS Effect (high dose)
- Depression, Headache, Dizziness

Anticholinergic effects (from atropine)
- Dry Mouth, Blurred vision, urinary retention

Question 4

Cholestyramine, Colestipol and Colesevalam

Answer 4

Type: Bile-acid sequestrants

MOA: Bind bile salts and some bacteria –> decrease unbound bile acids –> decrease fluid/electrolyte secretion

Use: Diarrhea caused by excess fecal bile acids (CD patients)

AES: Constipation, Bloating

DDIs: binds several drugs; separate by 2 hrs

Question 5

Bismuth subsalicylate and Bismuth subcitrate
potassium

Answer 5

Type: Bismuth

MOA: unknown, Direct antimicrobial effects, binds enterotoxin

Use: dyspepsia, H.pylori (Peptic ulcers)
Acute/travel diarrhea

AES: Black stools & tongue
Absorption of salicylate –> Reye’s syndrome

Question 6

Somatostatin

Answer 6

14-amino-acid peptide; found in the
hypothalamus, other parts of the CNS, the pancreas and in the GI tract

• Physiologic effects: “Master inhibitor”
  – Inhibits hormone secretion: Gastrin, cholecystokinin,
  vasoactive intestinal peptide, 5-HT
  – decrease Intestinal fluid secretion and pancreatic secretion
  – decrease GI motility
• Short half-life: 3 min (à no clinical relevance)

Question 7

Octreotide

Answer 7

Octapeptide analog of Somatostatin

Use: Diarrhea caused by hormone secreting tumors
(VIPoma, carcinoid)

PK:
t1/2 (i.v.) ≈ 1.5 h; t1/2 (s.c.) ≈ 6-12 h (Long-acting preparation: Octreotide enclosed in biodegradable microspheres)

AES:
– Short-term therapy: nausea, bloating or pain at
injection sites
– Long-term therapy: Gallstone formation and hypo- or hyperglycemia